The production of endogenous leukemia viruses (MuLV) in mice of high leukemic strains is controlled by multiple nonlinked dominant loci. Analysis by molecular hybridization demonstrates that in the AKR strain these loci (Akv-1 and Akv-2) are the integrated DNA proviruses of endogenous MuLV. The presence of genetically integrated "V" genes in mice of high leukemic strains results in the constitutive production of high titers of MuLV throughout their life span. Although persistent expression of MuLV is a characteristic of high leukemic strains, the development of overt leukemia in these mice does not occur until approximately one year of age. This delay in the onset of disease is one of the outstanding enigmas in the understanding of leukemogenesis. Thymus cells of preleukemic and leukemic AKR mice express on their cell surface elevated levels of antigens associated with the MuLV proteins gp70 and p30. The expression of these viral-coded proteins on the cell surface of thymocytes varies both quantitatively with the age of the mouse and qualitatively with the cellular populations that express these antigens. In this research proposal we intend to preparatively isolate cell populations from the thymuses of aged AKR mice according to their expression of MuLV-coded proteins. Studies will be performed to determine: (a) whether these cells represent preleukemic thymocytes, and (b) the thymus cell subpopulations from which these cells were derived.